The disease known as polyposis coli (adenomatous polyposis or familial polyposis) provides an excellent model for the study of both adenomas and cancers of the large bowel when these present as adenomas and isolated lesions of the large bowel (7). In both settings, adenomas may be reversible. Antioxidants retard experimental carcinogenesis, and administration of an antioxidant, ascorbic acid, to a few patients with polyposis coli was associated with a reduction in the number and size of adenomas in some. These results, which have been duplicated, must be explained by either a pharmacologic effect or a cyclic variation in adenomas independent of drug. Either alternative is important enough to merit investment of resources for an answer. In the proposed investigation, a randomized, double blind study of ascorbic acid or placebo will be performed in approximately 40 polyposis patients at St. Mark's Hospital, London, U.K. St. Mark's Hospital is the only hospital in the world with access to a sufficient number of patients for a definitive Phase III study, the long-term objective of which is the chemoprevention of large bowel cancer.